Periodontal innate immune mechanisms relevant to atherosclerosis

Atherosclerosis is a common cardiovascular disease in the USA where it is a leading cause of illness and death. Atherosclerosis is the most common cause for heart attack and stroke. Most commonly, people develop atherosclerosis as a result of diabetes, genetic risk factors, high blood pressure, a high‐fat diet, obesity, high blood cholesterol levels, and smoking. However, a sizable number of patients suffering from atherosclerosis do not harbor the classical risk factors. Ongoing infections have been suggested to play a role in this process. Periodontal disease is perhaps the most common chronic infection in adults with a wide range of clinical variability and severity. Research in the past decade has shed substantial light on both the initiating infectious agents and host immunological responses in periodontal disease. Up to 46% of the general population harbors the microorganism(s) associated with periodontal disease, although many are able to limit the progression of periodontal disease or even clear the organism(s) if infected. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. This review focuses on exploring the molecular consequences of infection by pathogens that exacerbate atherosclerosis, with the focus on infections by the periodontal bacterium Porphyromonas gingivalis as a running example.     

Subgingival microbial profile of obese women with periodontal disease

1 Background

This study compared the composition of subgingival microbiota between obese and non‐obese women with or without periodontal disease.

2 Methods

Full‐mouth periodontal clinical assessments were carried out in 76 obese women (17 periodontally healthy and 59 with periodontal disease), and 34 non‐obese women (12 periodontally healthy, 22 with periodontal disease). Subgingival biofilm samples were individually obtained from seven sites of each individual, and the prevalence and counts of 40 bacterial taxa were determined by the checkerboard method. The frequency and counts of each species were computed for each individual and across the groups. Differences among and between groups were sought by the Kruskal‐Wallis and Mann‐Whitney tests, respectively. Possible correlations between obesity and clinical and microbiologic parameters were tested with Spearman correlation coefficient.

3 Results

Streptococcus sanguinis, Streptococcus oralis, and Capnocytophaga ochracea were found in significantly higher levels in obese compared with non‐obese women (P < 0.01). In patients with periodontal health, Porphyromonas gingivalis and Leptotrichia buccalis were detected in higher mean frequency and/or counts in obese women than in non‐obese women, whereas in patients with periodontal disease, obese women harbored greater levels of C. ochracea than non‐obese women (P < 0.01). Moreover, obese women with periodontal disease presented significantly greater mean counts of P. gingivalis and Tannerella forsythia than non‐obese women with periodontal health (P < 0.01). When the conditions obesity and periodontal disease are present at the same time, significant positive correlations were detected with C. ocharcea, P. gingivalis, S. sanguinis, and T. forsythia.

4 Conclusion

Few differences in the composition of the subgingival microbiota of obese and non‐obese women with periodontal health or disease were found. However, a high prevalence of P. gingivalis in obese women with periodontal health was observed.     

Influence of periodontitis and scaling and root planing on insulin resistance and hepatic CD36 in obese rats

1 Background

The aim of the study was to explore the influence of periodontitis and scaling and root planing (SRP) on insulin resistance and hepatic CD36 in obese rats with periodontitis.

2 Methods

Thirty‐two specific pathogen free Sprague‐Dawley rats were randomly divided into four groups of eight animals each as follows: healthy rats (healthy group), obese rats (obesity group), obese rats with periodontitis (non‐therapy group), and obese rats with periodontitis who underwent periodontal SRP (therapy group). Rats were fed with a high‐fat diet for 16 weeks to build an obesity model. Periodontal inflammation was induced by performing periodontal ligation with Porphyromonas gingivalis. The tissue around the maxillary second molars, bilaterally, were collected. The periodontal attachment level (from the cemento‐enamel junction to the bottom of the periodontal pocket) of the second molars was measured in all groups. All rats were subjected to fasting blood glucose, insulin, and serum C‐reactive protein tests (CRP). Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA‐IR), oral glucose tolerance test (OGTT), and area under the curve (AUC). The liver was excised to detect intrahepatic free fatty acid (FFA) levels and pathologic observation. Real‐time quantification PCR, western blot, and immunohistochemistry were applied to detect hepatic CD36 expression.

3 Results

Compared with the obesity group, HOMA‐IR, AUC, intrahepatic FFA, and protein expression, and mRNA levels of hepatic CD36 in the non‐therapy group were significantly increased (P < 0.05). HOMA‐IR, AUC, CRP, protein expression, and mRNA levels of hepatic CD36 were all significantly decreased (P < 0.05) 2‐weeks after SRP.

4 Conclusions

Periodontitis increases insulin resistance while scaling and root planning could improve insulin resistance. Hepatic CD36 regulation may be considered a potential mechanism for this phenomenon.     

Effect of being overweight and obese on periodontal treatment costs

BackgroundObesity can increase a person’s risk of developing periodontal disease, and patients with obesity have greater health care costs. However, the effect of obesity on periodontal treatment costs has not been examined.MethodsThis retrospective cohort study used data from the electronic dental records of adult patients examined from July 1, 2010, through July 31, 2019 at a US dental school. Primary exposure was body mass index, which was categorized as obese, overweight, or normal. Periodontal disease was categorized using clinical probing measures. Fee schedules and procedure codes were used to compute the primary outcome, which was total periodontal treatment costs. A generalized linear model with gamma distribution was used to examine the relationship between body mass index and periodontal costs after controlling for initial periodontal disease severity and other confounding variables. Parameter coefficients and mean ratios with 95% CIs were estimated.ResultsThe study sample included 3,443 adults, of whom 39% were normal weight, 37% were overweight, and 24% were obese. Mean (SD) total periodontal treatment costs for patients who were obese were considerably higher ($420 [$719]) than those for patients who were overweight ($402 [$761]) and patients who were normal weight ($268 [$601]). After controlling for covariates and disease severity, patients who were obese had 27% higher periodontal treatment costs than patients who were normal weight. The additional periodontal treatment costs attributable to obesity were greater than those attributable to either diabetes or smoking.ConclusionsThe study results suggest that among patients at a dental school, those who were obese incurred substantially higher periodontal treatment costs than patients who were normal weight, independent of initial periodontal disease severity.Practical ImplicationsThe study findings have important implications for clinical guidelines and dental benefit design and coverage policies.     

The role of obesity as a modifying factor in patients undergoing non-surgical periodontal therapy

Background: Earlier studies have shown an association between obesity and periodontitis, which is mediated by cytokine production. The aim of this study is to assess the role of obesity as a modifying factor on periodontal clinical parameters and on circulating proinflammatory cytokine levels in subjects undergoing non‐surgical periodontal treatment. Methods: Twenty‐seven obese subjects and 25 normal‐weight subjects were enrolled in this study. Subjects in both groups had generalized chronic periodontitis. The periodontal parameters measured before and 3 months after non‐surgical periodontal therapy were: visible plaque index, bleeding gingival index, bleeding on probing, probing depth, and clinical attachment level. In addition, subjects underwent anthropometric measurements and serum analyses of fasting glucose, glycated hemoglobin, interleukin‐1β, interleukin‐6, tumor necrosis factor‐α, and interferon‐γ. Results: Periodontal therapy significantly decreased visible plaque index, bleeding gingival index, bleeding on probing, probing depth of 4 to 6 mm, probing depth ≥7 mm, clinical attachment level of 4 to 6 mm, and clinical attachment level ≥7 mm in both groups (P ≤0.05). Circulating proinflammatory cytokines significantly decreased in obese and normal‐weight subjects after periodontal treatment (P ≤0.05). However, interleukin‐6 and tumor necrosis factor‐α levels remained higher in obese subjects 3 months after treatment (P ≤0.05). Conclusion: Obesity does not seem to play a negative role by interfering in the improvement of the periodontal clinical response or decreasing circulating proinflammatory cytokine levels after periodontal treatment.     

Effect of Periodontitis on Adiponectin,C‐Reactive Protein,and Immunoglobulin G Against Porphyromonas gingivalis in Thai People With Overweight or Obese Status

Background: Obesity and periodontitis are associated with an inflammatory background. Inflammatory mediators involved may have reciprocal effects on one another. In this study, the levels of inflammatory mediators implicated in overweight or obese status and periodontitis are simultaneously evaluated. Methods: Body mass index (BMI) and waist circumference, periodontal disease status, and plasma levels of adiponectin, leptin, intercellular adhesion molecule (ICAM)‐1, vascular cell adhesion molecule 1, C‐reactive protein (CRP), immunoglobulin (Ig)G antibody against Porphyromonas gingivalis, and IgG against Aggregatibacter actinomycetemcomitans in 109 periodontitis participants with various BMIs were measured. BMI ≥23.0 kg/m² was considered overweight or obese. Results: Plasma adiponectin was decreased (P = 0.04), whereas CRP and IgG against P. gingivalis were increased (P = 0.04 and P = 0.001, respectively) in patients with severe periodontitis compared with patients with mild or moderate periodontitis, independent of overweight or obese status. Plasma CRP, ICAM‐1, and leptin were increased (P <0.001, P = 0.007, and P <0.001, respectively) and adiponectin was decreased (P = 0.04) in overweight or obese participants compared with normal weight participants, without influence of periodontitis severity. No interaction effect between periodontitis and overweight or obese status existed for these protein levels after the data were adjusted for age, sex, plasma levels of triglycerides, high‐density lipoprotein cholesterol, fasting plasma glucose, and blood pressure (P = 0.48). Conclusions: Periodontitis and overweight or obese BMI change plasma levels of the inflammatory mediators adiponectin and CRP, independently. This study suggests a role of periodontitis in systemic inflammatory response in Thai people who are overweight or obese.     

Does periodontal treatment have an effect on clinical and immunological parameters of periodontal disease in obese subjects? A systematic review and meta-analysis

Aim

The aim of this study was to systematically review the literature to answer the questions: (i) “Is periodontal treatment effective to improve clinical and immunological conditions in obese subjects?”; (ii) “Do obese subjects present different clinical and immunological response after periodontal therapy when compared to non-obese subjects?”

Methods

Searches were performed in six databases up to August 2014. Interventional studies were included if the following data were described: (1) Obesity/overweight assessment; (2) definition of periodontal disease; (3) periodontal therapy; (4) inflammatory marker in serum/plasma, and/or clinical parameters of periodontal disease. Assessment of quality was performed with the Downs and Black scale. Meta-analyses were conducted with the available data.

Results

Of 489 articles, 5 were included, and only 3 proceeded to meta-analysis of clinical outcomes. Included studies presented fair methodological quality. Statistical analysis demonstrated that periodontal therapy in obese subjects was effective to improve clinical outcomes. No clinical differences between post-therapy results of obese and non-obese were observed. Effects of periodontal therapy on inflammatory markers remain unclear.

Conclusions

Periodontal treatment seems to be effective to improve healing in obese individuals. No differences on periodontal healing between obese and non-obese subjects were observed; however, only limited and fragile base of evidence was available for analysis.

Clinical relevance

Periodontal treatment is effective to improve clinical and immunological periodontal parameters in adults. Also, obesity seems to not modify the periodontal healing after treatment.

     

Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early Rheumatoid Arthritis: A Cross‐Sectional Study

Background: Recent consensus emphasizes the importance of studying individuals at risk for rheumatoid arthritis (pre‐RA) and those with early RA (eRA). Periodontal tissues have been recently evaluated, but these studies are limited. To evaluate the periodontal condition, immunoglobulin (Ig)G subclasses against Porphyromonas gingivalis in individuals with pre‐RA and eRA were compared with controls to establish an association between periodontal infection markers and rheumatic activity. Methods: Rheumatologic and periodontal condition was evaluated in 119 individuals with pre‐RA, 48 patients with eRA, and matched controls. P. gingivalis IgG1 and IgG2 were analyzed. C‐reactive protein, erythrocyte sedimentation rate (ESR), rheumatoid factor, anticitrullinated protein antibodies (ACPAs), and RA activity were measured. The groups were compared with McNemar test and paired t‐test. Conditional logistic regression was performed for pre‐RA confounders, and χ² test was used to evaluate periodontal variables and RA activity indices. Results: Pre‐RA individuals showed significantly higher levels of plaque index (P = 0.01) and bleeding on probing (P = 0.03) and higher severity of periodontal disease (P = 0.02). Periodontitis was associated with pre‐RA (odds ratio, 3.39; 95% confidence interval, 1.64 to 7.01) but not with eRA. In pre‐RA, P. gingivalis–specific IgG2 was associated with ACPAs (P = 0.049) and disease severity visual analog scale (P = 0.03). In eRA, IgG2 against P. gingivalis was associated with ESR (P = 0.046) and ACPAs (P = 0.04). P. gingivalis was associated with ACPAs (P = 0.04). Conclusions: This study shows that individuals with pre‐RA have significant inflammatory periodontal involvement. There was a significant association between IgG against P. gingivalis and ACPAs in pre‐RA and markers of RA activity in individuals with eRA.     

In vivo expression of proteases and protease inhibitor,a serpin,by periodontal pathogens at teeth and implants

Porphyromonas gingivalis and Tannerella forsythia secrete proteases, gingipains and KLIKK‐proteases. In addition, T. forsythia produces a serpin (miropin) with broad inhibitory spectrum. The aim of this pilot study was to determine the level of expression of miropin and individual proteases in vivo in periodontal and peri‐implant health and disease conditions. Biofilm and gingival crevicular fluid (GCF)/ peri‐implant sulcular fluid (PISF) samples were taken from healthy tooth and implant sites (n = 10), gingivitis and mucositis sites (n = 12), and periodontitis and peri‐implantitis sites (n = 10). Concentration of interleukin‐8 (IL‐8), IL‐1β and IL‐10 in GCF was determined by enzyme‐linked immunosorbent assay. Loads of P. gingivalis and T. forsythia and the presence of proteases and miropin genes were assessed in biofilm by quantitative PCR, whereas gene expression was estimated by quantitative RT‐PCR. The presence of P. gingivalis and T. forsythia, as well as the level of IL‐8 and IL‐1β, were associated with disease severity in the periodontal and peri‐implant tissues. In biofilm samples harboring T. forsythia, genes encoding proteases were found to be present at 72.4% for karilysin and 100% for other KLIKK‐protease genes and miropin. At the same time, detectable mRNA expression of individual genes ranged from 20.7% to 58.6% of samples (for forsylisin and miropsin‐1, respectively). In comparison with the T. forsythia proteases, miropin and the gingipains were highly expressed. The level of expression of gingipains was associated with those of miropin and certain T. forsythia proteases around teeth but not implants. Cumulatively, KLIKK‐proteases and especially miropin, might play a role in pathogenesis of both periodontal and peri‐implant diseases.     

The GroEL protein of Porphyromonas gingivalis accelerates tumor growth by enhancing endothelial progenitor cell function and neovascularization

Porphyromonas gingivalis is a bacterial species that causes destruction of periodontal tissues. Additionally, previous evidence indicates that GroEL from P. gingivalis may possess biological activities involved in systemic inflammation, especially inflammation involved in the progression of periodontal diseases. The literature has established a relationship between periodontal disease and cancer. However, it is unclear whether P. gingivalis GroEL enhances tumor growth. Here, we investigated the effects of P. gingivalis GroEL on neovasculogenesis in C26 carcinoma cell‐carrying BALB/c mice and chick eggs in vivo as well as its effect on human endothelial progenitor cells (EPC) in vitro. We found that GroEL treatment accelerated tumor growth (tumor volume and weight) and increased the mortality rate in C26 cell‐carrying BALB/c mice. GroEL promoted neovasculogenesis in chicken embryonic allantois and increased the circulating EPC level in BALB/c mice. Furthermore, GroEL effectively stimulated EPC migration and tube formation and increased E‐selectin expression, which is mediated by eNOS production and p38 mitogen‐activated protein kinase activation. Additionally, GroEL may enhance resistance against paclitaxel‐induced cell cytotoxicity and senescence in EPC. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to the neovasculogenesis of tumor cells and resulting in accelerated tumor growth.     

Inhibition of Porphyromonas gingivalis‐induced periodontal bone loss by CXCR4 antagonist treatment

Microbial pathogens have evolved mechanisms to proactively manipulate innate immunity, thereby improving their fitness in mammalian hosts. We have previously shown that Porphyromonas gingivalis exploits CXC‐chemokine receptor‐4 (CXCR4) to instigate a subversive crosstalk with Toll‐like receptor 2 that inhibits leukocyte killing of this periodontal pathogen. However, whether CXCR4 plays a role in periodontal disease pathogenesis has not been previously addressed. Here, we hypothesized that CXCR4 is required for P. gingivalis virulence in the periodontium and that treatment with AMD3100, a potent CXCR4 antagonist, would inhibit P. gingivalis‐induced periodontitis. Indeed, mice given AMD3100 via osmotic minipumps became resistant to induction of periodontal bone loss following oral inoculation with P. gingivalis. AMD3100 appeared to act in an antimicrobial manner, because mice treated with AMD3100 were protected against P. gingivalis colonization and the associated elevation of the total microbiota counts in the periodontal tissue. Moreover, even when administered 2 weeks after infection, AMD3100 halted the progression of P. gingivalis‐induced periodontal bone loss. Therefore, AMD3100 can act in both preventive and therapeutic ways and CXCR4 antagonism could be a promising novel approach to treat human periodontitis.     

Activation of inflammasomes in dendritic cells and macrophages by Mycoplasma salivarium

Interleukin‐1β (IL‐1β) plays crucial roles in the pathogenesis of periodontal disease. It is produced after the processing of pro‐IL‐1β by caspase‐1, which is activated by the inflammasome‐a multiprotein complex comprising nucleotide‐binding domain leucine‐rich repeat‐containing receptor (NLR), the adaptor protein apoptosis‐associated speck‐like protein containing a caspase‐recruitment domain (ASC), and procaspase‐1. Mycoplasma salivarium preferentially inhabits the gingival sulcus and the incidence and number of organisms in the oral cavity increase significantly with the progression of periodontal disease. To initially clarify the association of this organism with periodontal diseases, this study determined whether it induces IL‐1β production by innate immune cells such as dendritic cells or macrophages by using Mycoplasma pneumoniae as a positive control. Both live and heat‐killed M. salivarium and M. pneumoniae cells induced IL‐1β production by XS106 murine dendritic cells as well as pyroptosis. The activities were significantly downregulated by silencing of caspase‐1. Bone‐marrow‐derived macrophage (BMMs) from wild‐type and NLR‐containing protein 3 (NLRP3)‐, ASC‐, and caspase‐1‐deficient mice were examined for IL‐1β production in response to these mycoplasmas. Live M. salivarium and M. pneumoniae cells almost completely lost the ability to induce IL‐1β production by BMMs from ASC‐ and caspase‐1–deficient mice. Their activities toward BMMs from NLRP3‐deficient mice were significantly but not completely attenuated. These results suggest that live M. salivarium and M. pneumoniae cells can activate several types of inflammasomes including the NLRP3 inflammasome. Both M. salivarium and M. pneumoniae cells can activate THP‐1 human monocytic cells to induce IL‐1β production. Hence, the present finding that M. salivarium induces IL‐1β production by dendritic cells and macrophages may suggest the association of this organism with periodontal diseases.     

Immunomodulation of dendritic cells differentiated in the presence of nicotine with lipopolysaccharide from Porphyromonas gingivalis

Tobacco smoking is a significant risk factor for periodontal diseases. Nicotine, one of the most studied constituents in cigarette smoke, is thought to modify immune responses. Dendritic cells (DCs), which are key mediators between innate and adaptive immunity, stimulate naive T cells to differentiate to effector T‐cell subsets that may be actively involved in the immunopathogenesis of periodontal diseases. In this study, we evaluated the effects of nicotine and lipopolysaccharide (LPS) from Porphyromonas gingivalis, alone and in combination, on the functions of human monocyte‐derived DCs to elucidate the mechanism of tissue destruction of smoking‐associated periodontal diseases. P. gingivalis LPS‐stimulated DCs differentiated with nicotine (NiDCs) induced lower T‐cell proliferation and human leukocyte antigen (HLA)‐DR expression, but elevated expression of programmed cell death ligand 1. Additionally, NiDCs impaired interferon‐γ production but maintained interleukin (IL)‐5 and IL‐10 production in co‐cultured T cells. Furthermore, NiDCs produced lower levels of proinflammatory cytokines compared with DCs differentiated in the absence of nicotine. Interestingly, NiDCs preferentially produced the T helper 2 (Th2)‐type chemokines macrophage chemotactic protein‐1 and macrophage‐derived chemokine. These results suggest that the presence of nicotine during differentiation of DCs modulates the immunoregulatory functions of P. gingivalis LPS‐stimulated DCs.     

Interferon‐Gamma and Fas Are Involved in Porphyromonas gingivalis–Induced Apoptosis of Human Extravillous Trophoblast‐Derived HTR8/SVneo Cells via Extracellular Signal‐Regulated Kinase 1/2 Pathway

Background: A number of studies recently revealed a link between periodontal disease and preterm birth (PTB). PTB can be induced by dental infection with Porphyromonas gingivalis (Pg), a periodontopathic bacterium. This study aims to investigate responses of human extravillous trophoblast‐derived HTR8/SVneo cells to Pg infection. Methods: Cell apoptosis, cell viability, protein expression, and cytokine production in HTR8 cells were measured via: 1) flow cytometry, 2) CCK‐8 assay, 3) western blot, and 4) enzyme‐linked immunosorbent assay methods, respectively. Results: Pg decreased cell viability and increased cell apoptosis, active caspase‐3 and Fas expression, and interferon‐gamma (IFN‐γ) secretion in HTR8 cells. Extracellular signal‐regulated kinase (ERK) 1/2 inhibitor U0126 and FasL neutralizing antibody NOK1 that blocks FasL/Fas interaction both significantly suppressed Pg‐induced apoptosis. U0126 also inhibited IFN‐γ secretion and Fas expression close to control levels. Moreover, treatment with recombinant IFN‐γ also significantly decreased number of viable HTR8 cells and increased Fas expression, suggesting IFN‐γ may play an important role in Pg‐induced apoptosis of HTR8 cells, at least partially through regulation of Fas expression. Conclusions: To the best of the authors’ knowledge, this is the first study to demonstrate Pg induces IFN‐γ secretion, Fas expression, and apoptosis in human extravillous trophoblast‐derived HTR8/SVneo cells in an ERK1/2‐dependent manner, and IFN‐γ (explored by recombinant IFN‐γ) and Fas are involved in Pg‐induced apoptosis. The finding that Pg infection abnormally regulates inflammation and apoptosis of human trophoblasts may give new insights into the possible link of PTB with maternal periodontal disease and periodontal pathogens.     

Obesity and Cumulative Inflammatory Burden: A Valuable Risk Assessment Parameter in Caring for Dental Patients

A new model of risk assessment that recognizes the importance of reducing patients' cumulative inflammatory burden by targeting overweight and obesity, in individuals with periodontal disease, may be a valuable risk assessment parameter in caring for dental patients.BackgroundThe growing body of evidence that suggests obesity, Metabolic Syndrome and periodontal disease are interrelated offers an unprecedented opportunity to adopt a new model of risk assessment that has the potential to beneficially influence not only the periodontal health of obese and overweight patients, but simultaneously may also reduce a person's overall risk for developing heart disease and type 2 diabetes, and perhaps other inflammatory driven disease states.MethodsThis paper presents an overview of research that builds the case for a new model of risk assessment that focuses on the cumulative inflammatory burden that may be elevated by the presence of periodontal disease in obese patients. In addition, the biological plausibility of the concepts of inflammatory priming and inflammatory loading is discussed, and several simple ideas are suggested for identifying at-risk patients.ConclusionsGiven the significant rise in obesity and the impact that obesity has on periodontal health and other inflammatory driven, systemic disease states, adoption of a new model of risk assessment is suggested–one that considers an individual's cumulative inflammatory burden which may be amplified as a result of coexisting obesity and other components of Metabolic Syndrome and periodontal disease. Knowledge gathered thus far combined with further clinical research must be translated into better ways to treat and maintain obese periodontal patients. These measures may pave the way for prevention of metabolic diseases and obesity with a relevant impact on patients' periodontal status.     

Analysis of the complement sensitivity of oral treponemes and the potential influence of FH binding,FH cleavage and dentilisin activity on the pathogenesis of periodontal disease

Treponema denticola, a periopathogen, evades complement‐mediated killing by binding the negative complement regulatory protein factor H (FH) to its surface via the FhbB protein. Paradoxically, bound FH is cleaved by T. denticola's dentilisin protease, a process hypothesized to trigger localized dysregulation of complement activation in periodontal pockets. The ability of other oral treponemes to evade complement‐mediated killing and bind and cleave FH has not been assessed. In this report, we demonstrate that representative isolates of Treponema socranskii, Treponema medium, Treponema pectinovorum and Treponema maltophilum are also serum resistant, whereas Treponema vincentii and Treponema amylovorum are serum sensitive. Although T. denticola's ability to evade complement‐mediated killing is strictly dependent on FH binding, other serum‐resistant treponemal species lack FhbB and do not bind FH, indicating an FH‐independent mechanism of complement evasion. To assess the influence of FhbB sequence variation on FH binding and cleavage by T. denticola, fhbB sequences were determined for 30 isolates. Three distinct phyletic types were identified. All T. denticola strains bound FH and were serum resistant, but differences in binding kinetics, dentilisin activity and FH cleavage ability were observed. Based on these analyses, we hypothesize that the composition of the T. denticola population is a determining factor that influences the progression and severity of periodontal disease.